1. Field of the Invention
The present invention relates to butyrophenone transdermal compositions (hereinafter may be referred to as transdermal compositions) capable of inhibiting vomiting which occurs as an adverse side effect when chemotherapeutic drugs against cancer are administered.
2. Description of the Related Art
Vomiting which occurs as an adverse side effect when chemotherapeutic drugs against cancer are administered is a hindrance in achieving effective cancer treatment. In order to inhibit vomiting caused by the administration of chemotherapeutic drugs against cancer, countermeasures such as massive dose therapy using metoclopramide, combination use of a chemotherapeutic drug and asteroid hormone, and oral administration or injection of butyrophenones or serotonin antagonists have been practiced. However, massive dose therapy of metoclopramide and use of asteroid hormone in combination with other drugs are not very much useful because they involve drawbacks that antiemetic action is weak, and in addition, adverse side effects are caused. On the other hand, serotonin antagonists, which has recently been developed, causes less adverse side effects, but their antiemetic action is still unsatisfactory.
Since vomiting caused by anti-cancer drugs occurs not only during the period of drug administration but also during the suspension period of drugs, the antiemetic effect must last long enough. Conventional antiemetics, however, cannot maintain their effect successfully when they are dosed once a day. Accordingly, patients are forced to take the drugs 3 or even more times a day, or receive intravenous drip in a limited number of well-equipped institutions.
When a patient has vomiting by the use of an anti-cancer drug, antiemetics are hardly administered via oral route due to vomiting, and therefore, their effect cannot be expected. On the other hand, since chemotherapeutic drugs against cancer are generally administered by injection, further injection of antiemetics will bring more suffering to patients, and in addition, such injection involves limitation because it will not be performed in the home treatment.
Butyrophenones have already been used as a psychotropic drug. They have also been used, in the forms of oral or injection preparations, for preventing vomiting which occurs during use of anti-cancer drugs and have exhibited good results. They are, however, accompanied by a shortcoming of causing extrapyramidal side effect. Butyrophenones have a narrow range of concentrations in which the side effect and the primary vomiting-inhibitory action occur. It has therefore been difficult to maintain the drug concentration in blood where only vomiting-inhibitory action is obtained over a long period. Thus, drugs which contain a butyrophenone, which do not cause adverse side effects, and which exhibit lasting effect of vomiting inhibition have been desired. In this regard, patches in the form of films (Japanese Patent Application Laid-open (kokai) No. 232817/1991) and like products have already been developed. Tape articles and plasters of this type can reduce adverse side effects, but still involve drawbacks that severe rash may be induced.
Accordingly, drugs which make the best use of the potent vomiting inhibitory action of butyrophenones over a prolonged period, which are free from adverse side effects, and are dosed easily without causing any pain to patients have still been desired.
Under the above circumstances, the present inventors have carried out extensive studies in search of new transdermal compositions to solve the above-mentioned problems, and have found that when a water-soluble polymer which is obtained from a monomer containing, partly or wholly, aliphatic carboxylic acid having a polymerizable double bond or a salt of the carboxylic acid, a cross linking agent, a cross linking promoter, water, a butyrophenone drug, a solvent for the butyrophenone drug, and optionally a plasticizer, are combined and the pH of the combined material is adjusted to fall in the range of 5.5 to 8.0, an excellent transdermal composition can be obtained which is free from adverse side effects, which exhibits long-lasting vomiting inhibitory effect, and which does not cause rash or the like, leading to completion of the invention.